Differential Activation of TRP Channels in the Adult Rat Spinal Substantia Gelatinosa by Stereoisomers of Plant-Derived Chemicals.

Eiichi Kumamoto,Tsugumi Fujita

doi:10.3390/ph9030046

Abstract

Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of dorsal root ganglion (DRG) neuron increases the spontaneous release of l-glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons which play a pivotal role in regulating nociceptive transmission. The TRP channels are activated by various plant-derived chemicals. Although stereoisomers activate or modulate ion channels in a distinct manner, this phenomenon is not fully addressed for TRP channels. By applying the whole-cell patch-clamp technique to SG neurons of adult rat spinal cord slices, we found out that all of plant-derived chemicals, carvacrol, thymol, carvone and cineole, increase the frequency of spontaneous excitatory postsynaptic current, a measure of the spontaneous release of l-glutamate from nerve terminals, by activating TRP channels. The presynaptic activities were different between stereoisomers (carvacrol and thymol; (−)-carvone and (+)-carvone; 1,8-cineole and 1,4-cineole) in the extent or the types of TRP channels activated, indicating that TRP channels in the SG are activated by stereoisomers in a distinct manner. This result could serve to know the properties of the central terminal TRP channels that are targets of drugs for alleviating pain.

Highlights

Cation-permeable transient receptor potential (TRP) channels expressed in dorsal root ganglion (DRG) neurons are involved in nociceptive transmission from the periphery
The TRP ankyrin-1 (TRPA1) channel is found in a subset of rat DRG neurons in which it is co-expressed with the TRP vanilloid-1 (TRPV1), but not the TRP melastatin-8 (TRPM8) channel [2,3]
In the peripheral terminal of the DRG neuron, the TRPV1 channel is activated by capsaicin, protons and noxious heat (>43 ̋C; [6]; for review see [7]); the TRPA1 channel by pungent compounds in mustard, cinnamon and garlic (allyl isothiocyanate (AITC), cinnamaldehyde and allicin, respectively), and noxious cold temperature (

Summary

Spinal Substantia Gelatinosa Involved in Regulating Nociceptive Transmission

Nociceptive transmission in the SG is in origin monosynaptic from glutamatergic DRG neurons and polysynaptic from glutamate-, GABA- and/or glycine-containing interneurons [28]. Inhibition of the release of L-glutamate from nerve terminals onto rat SG neurons was produced by opioids ([49]; for review see [33]), nociceptin [50,51], baclofen [36,52,53], the endocannabinoid anandamide [16,54], norepinephrine [55], serotonin [30,40], adenosine ([41,56,57]; for a review see [43]) and galanin [48,58]

TRP Channels in Nociception

Actions of Thymol and Carvacrol

Findings

Conclusions